Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

C. Dive; R. A. Smith; E. Garner; T. Ward; S. S. George-Smith; F. Campbell; W. Greenhalf; P. Ghaneh; J. P. Neoptolemos

doi:10.1038/sj.bjc.6605494

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

C. Dive, R. A. Smith, E. Garner, T. Ward, S. S. George-Smith, F. Campbell, W. Greenhalf, P. Ghaneh, J. P. Neoptolemos

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-review

Abstract

Background:Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.Methods:Plasma samples from 103 patients with pancreatic cancer stored at 80 °C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l 1) compared with the locally advanced (n20; 748 (406-1150) U l 1) and resected (n64; 612 (331-987) U l 1) patients (P0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P0.001) but not multivariate (P0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P0.001) and the duration of plasma storage (P0.001).Conclusions:Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. © 2010 Cancer Research UK.

Original language	English
Pages (from-to)	577-582
Number of pages	5
Journal	British Journal of Cancer
Volume	102
Issue number	3
DOIs	https://doi.org/10.1038/sj.bjc.6605494
Publication status	Published - Feb 2010

Keywords

Apoptosis
Circulating biomarker
Cytokeratin 18
M30
M65
Necrosis
Pancreatic cancer

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.bjc.6605494

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title = "Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer",

abstract = "Background:Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.Methods:Plasma samples from 103 patients with pancreatic cancer stored at 80 °C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l 1) compared with the locally advanced (n20; 748 (406-1150) U l 1) and resected (n64; 612 (331-987) U l 1) patients (P0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P0.001) but not multivariate (P0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P0.001) and the duration of plasma storage (P0.001).Conclusions:Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. {\textcopyright} 2010 Cancer Research UK.",

keywords = "Apoptosis, Circulating biomarker, Cytokeratin 18, M30, M65, Necrosis, Pancreatic cancer",

author = "C. Dive and Smith, {R. A.} and E. Garner and T. Ward and George-Smith, {S. S.} and F. Campbell and W. Greenhalf and P. Ghaneh and Neoptolemos, {J. P.}",

year = "2010",

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doi = "10.1038/sj.bjc.6605494",

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pages = "577--582",

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T1 - Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

AU - Dive, C.

AU - Smith, R. A.

AU - Garner, E.

AU - Ward, T.

AU - George-Smith, S. S.

AU - Campbell, F.

AU - Greenhalf, W.

AU - Ghaneh, P.

AU - Neoptolemos, J. P.

PY - 2010/2

Y1 - 2010/2

N2 - Background:Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.Methods:Plasma samples from 103 patients with pancreatic cancer stored at 80 °C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l 1) compared with the locally advanced (n20; 748 (406-1150) U l 1) and resected (n64; 612 (331-987) U l 1) patients (P0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P0.001) but not multivariate (P0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P0.001) and the duration of plasma storage (P0.001).Conclusions:Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. © 2010 Cancer Research UK.

AB - Background:Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.Methods:Plasma samples from 103 patients with pancreatic cancer stored at 80 °C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l 1) compared with the locally advanced (n20; 748 (406-1150) U l 1) and resected (n64; 612 (331-987) U l 1) patients (P0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P0.001) but not multivariate (P0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P0.001) and the duration of plasma storage (P0.001).Conclusions:Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. © 2010 Cancer Research UK.

KW - Apoptosis

KW - Circulating biomarker

KW - Cytokeratin 18

KW - M30

KW - M65

KW - Necrosis

KW - Pancreatic cancer

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DO - 10.1038/sj.bjc.6605494

M3 - Article

SN - 0007-0920

VL - 102

SP - 577

EP - 582

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 3

ER -

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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